We seek to expand preliminary data which suggest that: a) the biosynthesis and metabolism of the polyamines, putrescine, spermidine, could play a key role in proper intestinal epithelial growth, regeneration and maturation; b) circulating diamine oxidase (histaminase) activity may serve as a monitor of small intestinal mucosal integrity; and c) abnormal circulating levels of one or more of the polyamines and/or diamine oxidase activity may provide a biochemical index for identifying cystic fibrosis heterozygotes. Ontogeny studies will be completed in the newborn rat intestinal mucosa for the appearance of polyamine synthesis (via ornithine decarboxylase) biogenic amine synthesis (via L-dopa decarboxylase, and diamine oxidase. A marked and transient "spike" in ornithine decarboxylase activity has been observed to precede by several days the appearance of mature biochemical functions in the intestine of the newborn rat. The functional significance of this "spike" will be assessed by selectively inhibiting ornithine decarboxylase for various time intervals. The consequences of these biochemical patterns for the regeneration of intestinal mucosa in adult rats (following injury induced by systemic arabinosyl cytosine and local hyperosmolar perfusion) will also be assessed. In all studies, polyamine levels will be measured in intestinal tissue and plasma as will circulating diamine oxidase activity. Activities of diamine oxidase and the decarboxylases will be measured by radioassay. Polyamines will be measured fluorometrically on an amino acid analyzer after separation by ion exchange chromatography. Each measurement will be related to the degree of intestinal injury and recovery. Finally, we will expand prospective studies which seek to establish further that abnormal circulating levels of one or more of the polyamines and/or of diamine oxidase activity, distinguish adult cystic fibrosis heterozygotes from age-matched normal adults.